Transient Calcium and Dopamine Increase PKA Activity and DARPP-32 Phosphorylation
Figure 9
Role of Altered Enzyme Quantities on the Integration Properties of DARPP-32
(A) Total concentrations of PKA, PP2B, PP2A, and cdk5 all are varied together between 0.1–10× the control level.
(A1) Independent of this variation, pairing of calcium and dopamine (red, squares) is more effective than either input alone (green dots or blue circles).
(A2) The basal levels of PKAc (black dashed line, triangles) as well as phosphoThr34 (black dotted line, triangles) vary with enzyme quantity. A decrease in enzyme quantity produces a decrease in the change of PKAc during stimulation (dashed line) and an increase in the phosphoThr34 levels (dotted line). Nonetheless, in all cases a simultaneous calcium and dopamine input is most effective in elevating both PKAc and phosphoThr34.
(B) The role of DARPP-32 in signal integration is independent of PKAc. Enzyme quantities were lowered to 10% of control and all the reaction rates in the PKA reactions were increased 100× to make the PKAc formation follow the cAMP signal more effectively.
(B1) The PKAc increase is slightly larger with dopamine alone and decreases almost to basal level in between transient dopamine pulses.
(B2) Thr34 phosphorylation increases with successive paired stimuli, and is higher for paired calcium and dopamine inputs.